A Cure for Vitamin B6 Deficiency

13 Oct 2015 --- In many tropical countries, particularly in sub-Saharan Africa, cassava is one of the most important staple foods. People eat the starchy storage roots but also the leaves as a vegetable. Both have to be cooked first to remove the toxic cyanide compounds that cassava produces.

Plant scientists at ETH Zurich and the University of Geneva have therefore set out to find a way to increase vitamin B6 production in the roots and leaves of the cassava plant. This could prevent vitamin B6 deficiency among people who consume mostly cassava.

Their project has succeeded: in the latest issue of Nature Biotechnology, the scientists present a new genetically modified cassava variety that produces several-fold higher levels of this important vitamin.

"Using the improved variety, only 500 g of boiled roots or 50 g of leaves per day is sufficient to meet the daily vitamin B6 requirement," says Wilhelm Gruissem, professor of plant biotechnology at ETH Zurich. The basis for the new genetically modified cassava variant was developed by Professor Teresa Fitzpatrick at the University of Geneva. She discovered the biosynthesis of vitamin B6 in the model plant thale cress (Arabidopsis thaliana). Two enzymes, PDX1 and PDX2, are involved in the synthesis of the vitamin. With the introduction of the corresponding genes for the enzymes, into the cassava genome, the researchers produced several new cassava lines that had increased levels of vitamin B6.

To determine if the increased production of the vitamin in the genetically modified cassava was stable without affected the yield, the plant scientists conducted tests in the greenhouse and in field trials over the course of several years. "It was important to determine that the genetically modified cassava consistently produced high vitamin B6 levels under different conditions," says Gruissem.

Measurements of the metabolites confirmed that cassava lines produced several times more vitamin B6 in both roots and leaves than normal cassava. The researchers also attributed the increased production to the activity of the transferred genes, regardless of whether the plants were grown in a greenhouse or the field. The increased vitamin B6 trait remained stable even after the cassava was multiplied twice by vegetative propagation.

Previously, the researchers had analysed several hundred different cassava varieties from Africa for its natural vitamin B6 content - none had a level as high as the genetically modified variety.

Vitamin B6 from the genetically modified varieties is bioavailable, which means that humans can absorb it well and use it, as was confirmed by a research team at the University of Utrecht.

"Our strategy shows that increasing vitamin B6 levels in an important food crop using Arabidopsis genes is stable, even under field conditions. Making sure that the technology is readily available to laboratories in developing countries is equally important," says Hervé Vanderschuren, who led the cassava research programme at ETH Zurich and recently became a professor of plant genetics at the University of Liège.

Vanderschuren hopes this can be performed in African laboratories. He has previously trained scientists on site and organized workshops to build platforms for the genetic modification of crop plants in African laboratories. "We hope that these platforms can help spread the technology to farmers and consumers." The method for increasing vitamin B6 has not been patented because the gene construct and technology should be available freely to all interested parties.

One huge hurdle, however, is the distribution and use of the new variety: "There are at least two obstacles: legislation for transgenic crops in developing countries and implementation of a cassava seed system to give all farmers access to technologies," says Vanderschuren.

Individual national organizations as well as the FAO and other NGOs are currently organizing the spread of cassava stem cuttings for cultivation in Africa. However, a better and more efficient organization for the distribution of healthy plant material is urgently needed, says the researcher.

On the legislative side, the cultivation of genetically modified cassava (and other crops) is not yet regulated everywhere. In numerous African countries, such as Uganda, Kenya and Nigeria, the governments have now enacted legislation for field trials of genetically modified plants. "This is an important step to ensure that improved varieties can be tested under field conditions," says Vanderschuren. "In order to allow the cultivation of genetically modified plants, the respective parliaments will have to develop further legislation."

There are many technical difficulties with GM crops and persuading consumers that they are safe to eat. Some concerns include:
1. Difficulties in deciding what is a healthy or safe level of some vitamins and minerals (which can be harmful at high levels or in some groups of people).
2. Unintended effects of altering plant pathways, such as increasing uptake of toxic metals from soils, making the plant more attractive to pests, or reducing its yield.
3. The limitations of a 'nutrient by nutrient' approach to tackling the problems caused by overeating or hidden hunger, both of which depend on altering whole diets.

Regulating health claims and safety for nutritionally-altered crops is expected to be particularly difficult because their impacts can depend on a wide variety of factors, including the soil that they are grown in and the diet of the person eating them.

Because GM technology introduces nutritional changes at the bottom of the food chain rather than in final, processed products, issues of traceability, liability and lack of reversibility arise. These issues may be particularly important for 'biofortified' staple crops, which could form a large proportion of people's diets, particularly in poor countries.